Wogonoside Attenuates Cutaneous Squamous Cell Carcinoma by Reducing Epithelial-Mesenchymal Transition/Invasion and Cancer Stem-Like Cell Property.

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the most common second basal cell carcinoma in our population. Wogonoside, the main in vivo metabolite of wogonin, possesses anti-inflammatory, anti-angiogenesis and anti-cancer activities. Nevertheless, the effectiveness of wogonoside therapy on cSCC has not been clarified. METHODS: In this study, we investigated the effects of wogonoside on cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) properties of SCL-1 and SCC12 cell lines, and the effects on tumor formation in vivo. In vitro, cells were treated with 0, 25, 50 and 100 µM wogonoside for 48 h. In vivo, SCL-1 cells were subcutaneously injected into the right thigh of mice to form xenograft tumors. Animals were randomly divided into two groups (n=10): the control group and the 80 mg/kg wogonoside group. RESULTS: The results showed that wogonoside attenuated proliferation, invasion and EMT of SCL-1 and SCC12 cell lines, and enhanced the rate of apoptosis. Meanwhile, wogonoside efficiently abolished the CSC traits of cSCC; the expression of CSC markers (ALDH1, SOX-2, Oct4 and CD44) and the percentage of CD133+ cells were remarkably downregulated. In addition, we found that wogonoside repressed the activation of both PI3K/AKT and Wnt/ß-catenin pathways. In vivo, wogonoside significantly inhibited tumor formation. CONCLUSION: The results indicated that wogonoside could attenuate cSCC by reducing EMT, invasion and CSC properties. The efficacy of intervention may be related to inhibition of the PI3K/Akt and Wnt/ß-catenin pathways. These novel findings could furnish new ideas on the potential therapeutic application of wogonoside in cSCC cancellation and cancer intervention.

Reduction of COX-2 through modulating miR-124/SPHK1 axis contributes to the antimetastatic effect of alpinumisoflavone in melanoma.

Alpinumisoflavone (AIF) is a naturally occurring flavonoid that is a major bioactive component of the medicinal plant Derris eriocarpa. In this study we evaluated the antimetastatic effect of AIF and investigated the underlying mechanism of action using in vitro and in vivo models of melanoma. We found that AIF impaired the metastatic potential of A375 and SK-MEL-1 human melanoma cells by promoting cell differentiation as assessed by melanin content, protoporphyrin IX accumulation, and tissue transglutaminase activity. In addition, AIF inhibited cell adhesion, migration, and invasion in melanoma cells. We found that AIF treatment decreased cyclooxygenase-2 (COX-2) expression, and COX-2 overexpression attenuated the inhibitory effects of AIF on the metastatic behaviors of melanoma cells. AIF dose-dependently increased microRNA-124 (miR-124) levels and decreased levels of sphingosine kinase 1 (SPHK1), a target of miR-124. In a mouse model of melanoma, AIF suppressed lung metastasis. Taken together, our findings suggest that AIF inhibits metastasis in melanoma by modulating COX-2 expression, at least in part, through targeting the miR-124/SphK1 axis. Our study provides evidence that AIF may be useful as an antimetastatic agent in the treatment of melanoma.

Transient bullous dermolysis of the newborn: a novel de novo mutation in the COL7A1 gene.

BACKGROUND: Bullous dermolysis of the newborn (BDN), an extremely rare clinical type of dystrophic epidermolysis bullosa (DEB), is characterized by subepidermal blistering at birth or shortly thereafter, followed by rapid improvement with minimal scarring or pigmentation. A total of 38 cases have been reported in the literature since the disease was initially described in 1985, but only 14 mutations in COL7A1, the gene responsible for the disease, have been detected in families with BDN. OBJECTIVES: We report a Chinese male infant with BDN and indirect inguinal hernia, in whom a novel de novo mutation in COL7A1 was demonstrated. METHODS: DNA was obtained from the blood of the patient and his parents. The coding exon and flanking regions of COL7A1 gene were amplified by polymerase chain reaction and subjected to sequence analysis. RESULTS: Sequencing showed a heterozygous substitution of guanine by adenine at nucleotide position 6136 of exon 73 in the triple helical domain of type VII collagen, which predicts a change of glycine by serine at position p.G2046S. The mutation was considered to be a pathogenic and de novo mutation. CONCLUSIONS: The coexistence of BDN and indirect inguinal hernia may simply be coincidental. These data contribute to the expanding database of COL7A1 mutations in DEB and should be useful for genetic counseling and prenatal diagnosis in affected families.